1. Field of the Invention
This invention relates to the use of oils containing triglycerides of essential fatty acids for inter alia topical and dietetic purposes, and to compositions comprising such oils.
2. Description of the Related Art
Triesters of glycerol are known as triglycerides or triacylglycerols. If the triglyceride is solid at room temperature, then it is generally considered to be a fat, whereas if it is liquid at room temperature, then it is generally considered to be an oil. Most triglycerides in animals are fats, while most triglycerides in vegetables tend to be oils. Fatty acids can be obtained from these fats or oils by hydrolysis. Certain fatty acids, called essential fatty acids, must be present in the human diet and are used in the body to synthesize, for example, prostaglandins. There are two main series of essential fatty acids: one is called the 3n family (also known as the z-3 family); and the other is called the n6 family (also known as the z-6 family).
Stearidonic acid (SA) is a polyunsaturated fatty acid of the n3 family; it is an essential fatty acid. Chemically, it can be described as 6c,9c,12c,15c-octadecatetraenoic acid or 18:4n3. Other essential fatty acids are linoleic acid (LA), a-linolenic acid (ALA) and c-linolenic acid (GLA)xe2x80x94these acids can be described as C18:2n6, C18:3n3 and C18:3n6, respectively. Stearidonic acid is found in marine oils, some plant oils and in lipids isolated from micro-organisms. It is also produced in the human body by the desaturation of a-linolenic acid (1 8:3n3) with the enzyme  less than xe2x88x926 desaturase. The metabolic transformation in the human body of n3 fatty acids by desaturation and elongation takes place as follows:
The activity of the enzyme  less than 6 desaturase is known to be of lower activity following certain illnesses, and in old age; its activity can also be lowered by poor diet and certain lifestyles. This is significant, because if the activity of  less than 6 desaturase is lowered, then the body""s capacity to make stearidonic acid (and the other compounds in the scheme shown above) is also lowered. One way to remedy this problem is to take a dietary supplement containing stearidonic acid.
It is known that the oils of the pips of certain fruits contain triglycerides of a number of fatty acids. In GB-A-2118567, it is disclosed that an oil extracted from the pips of the fruit of blackcurrants, redcurrants and gooseberries contain triglycerides of fatty acids in the proportions shown in Table 1.
However, none of the materials in Table 1 is very useful as a source of stearidonic acid, because this acid is present in such a low concentration. In order to use these materials as a source of stearidonic acid, it would be necessary either to use them in large quantities or to carry out expensive chemical processing to concentrate the stearidonic acid. Accordingly, there is a need for a material that is rich in stearidonic acid but that does not contain any toxic compounds.
A rich natural, non-toxic, source of stearidonic acid that can be used to make a wide range of dietetic, cosmetic, personal care and healthcare products is found in the oil of seeds of the Borignaceae family. However, we have surprisingly found that the oil itself can be used in dietetic, cosmetic, personal care and healthcare products, without the need for additional treatment or purification, and having advantages over the purified stearidonic acid.
In one aspect, the invention provides the use of an oil extracted from seeds of the Borignaceae family in topical application to, or oral ingestion by, the human or animal body. This oil alone may be used for these purposes or, preferably, it is used to form a part of a composition e.g. for topical application to, or oral ingestion by, the human or animal body.
In an especially advantageous embodiment, the seeds are of the genus Echium; in particular, we have found that the seeds of Echium vulgaris and Echium plantagineum are very useful, especially E. plantagineum. 
Oil extracted from the seeds of the Borignaceae family contains the triglyceride of stearidonic acid. This is described in greater detail in our co-pending U.S. patent application Ser. No. 09/308,928, filed May 27, 1999, which is a 35 USC xc2xa7371 National Stage of PCT patent application filed Jun. 3, 1997, entitled xe2x80x9cVegetable Oil Compositionxe2x80x9d (PCT/GB97/01497), the entire disclosure of which is herein incorporated by reference.
In general, the oil contains stearidonic acid (in the form of the triglyceride) in an amount greater than 5wt %, preferably greater than 5.5wt %, more preferably greater than 10wt %, and most preferably greater than 15wt %; the oil may contain as much as 20wt % stearidonic acid, or more. The oil can be obtained at these concentrations without carrying out any purification process to increase the concentration of stearidonic acid in the oil. The compositions of three oils obtained from the seeds of the Borignaceae family have been analysed, and found to have fatty acids present (in the form of triglycerides) in the amounts shown in Table 2.
Moreover, we have surprisingly found that these oils are especially advantageous in their ability to inhibit UVB-induced release of PGE2: Ultraviolet (UV) light in the wavelength range of 290nm to 340 nm is covered by the range UVB (290nm to 320nm) and UVA2 (320nm to 340nm); UV light in this range is erythemognic. Exposure to small amount of UVB can be beneficial, since it is required for synthesis of vitamin D in the skin. However, larger amounts of UV radiation cause sunburn, which is characterised by erythema, pain swelling and blistering; in extreme cases there is epidermal necrosis.
Sunburn is a classical cutaneous inflammation whose pathogenesis is not completely understood. The release of inflammatory mediators including eicosanoids and cytokines seems to be important. UVB exposure can also compromise the immune system. Chronic UV exposure results in accelerated skin aging called photo-aging; it can also lead to the development of skin cancer. The major target in UV-induced carcinogenesis is probably DNA. However, the suppressed immune system could play an important role in the pathogenesis of these neoplasms. In addition to necrosis induced by UV exposure, there is evidence that even acute exposure can result in apoptosis (programmed cell death) of affected keratinocytes.
Cutaneous inflammation caused by UVB is mediated by various cytokines such as tumour necrosis factor-alpha (TNFa) and interleukin 1a (IL1a). In addition, UVB induces the release of arachidonic acid from cell membrane phospholipids, which is oxidised via the lipoxygenase and cyclo-oxgenase pathways to inflammatory metabolites; examples of these include leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). Since human keratinocytes lack the components to produce LTB4, PGE2 is probably the more important inflammatory metabolite in epidermis.
Therefore, these Borignaceae oils (and derivatives thereof) are useful for treating skin inflammation, particularly skin inflammation caused by radiation, such as UV radiation. They are particularly useful in treating bums, particularly first degree burns such as sunburn; they can also be used prophylactically as part of a sunscreen composition. Broadly, the invention may be applied to treat skin irritation caused by over-exposure to a wide variety of radiation, including UV radiation, infrared radiation, and radiation used during chemotherapy.
The oil extract can be used in a wide variety of topical applications, including many cosmetic and dermatological applications. The oil extract itself, or compositions formed from the oil extract, can be used to treat a wide variety of skin disorders, such as dry skin, itchy skin, psoriasis, eczema and the like. For example, the oil extract can be used in skin creams and emulsions, including cleansers, moisturising creams and sunscreens; shampoos; and bath oils.
Accordingly, there is provided a composition for topical application by the human or animal body, comprising an oil extracted from the seeds of the Borignaceae family, or a physiologically acceptable derivative thereof, in combination with a physiologically acceptable carrier therefor. The precise nature of the carrier depends on the use desired for the composition. In addition, the carrier would usually contain other active ingredients, such as moisturiser (e.g. for moisturising cream), a surfactant (e.g. for shampoo) or a UV-blocking/absorbing compound (e.g. for a sun-cream). Some specific examples of suitable carriers are disclosed in the Examples below.
According to one aspect of the invention, there is provided a sunscreen composition comprising an oil according to the invention containing stearidonic acid, or a physiologically acceptable derivative thereof, in combination with a UV blocking and/or UV-absorbing material. The term xe2x80x9csunscreen compositionxe2x80x9d as used in this specification includes materials that substantially completely block UV radiation and includes materials that only partially block UV radiation
It is particularly preferred that the sunscreen composition includes one or more of a moisturiser, an emollient, an emulsifier, a preservative, a dispersant, a viscosity modifier, a herbal extract, a solvent, a chelating agent, an antioxidant, a water-proofing agent, apH adjuster, a perfume, and a protein.
It is particularly preferred that the sunscreen composition includes one or more of titanium dioxide; zinc oxide; benzophenone-3; benzophenone-4; octyl methoxycinnamate (Parsol 1789); 3,3,5-trimethycyclohexyl salicylate; carbomer; hydroxeyethyl cellulose; lanolin alcohols; cetyl phosphate; fatty alcohols; C,12 to C15 alkyl benzoate; cyclomethicone; caprylic/capric triglycerides; mineral oil; glycerin; vitamin E; and isopropyl myristate.
The precise formulation of the sunscreen composition depends on the form required for the composition. Broadly, it may be in the form of a solid or a liquid suitable for topical application. Typically, the composition is provided in the form of a cream, an emulsion or a gel; however, the composition may be provided in other forms, such as a solid stick.
According to another aspect of the invention, we provide a pharmaceutical composition for treating skin inflammation caused by burns, by exposure to sunlight or by exposure to UV radiation, comprising an oil according to the invention containing stearidonic acid or a physiologically acceptable derivative thereof, and a physiologically acceptable carrier.
The carrier will include materials normally present in formulations for treating burns, such as antiseptic compounds, emollients, inorganics, humectants, moisturisers, anti-inflammatory agents, vitamins, preservatives, pH adjusters, proteins, herbal extracts, carriers/solvents, soothing/cooling agents, antioxidants, perfumes, emulsifiers and viscosity modifiers. Specific examples of useful materials include glycerine, triethanolamine stearate, vitamin E, lanolin, zinc oxide, allantoin, calamine, sodium lactate, water, lactic acid, pro-vitamin B5 and menthol.
The formulation of the carrier also depends on the form required for the pharmaceutical composition. Broadly, the pharmaceutical composition may be in the form of a solid or a liquid suitable for topical application. Typically, the pharmaceutical composition is provided in the form of a cream, an emulsion or a gel; however, the pharmaceutical composition may be provided in other forms, such as a solid stick.
The amount of the stearidonic acid (or derivative) in the sunscreen composition or the pharmaceutical composition depends upon the way the composition is to be used. However, the compositions according to the invention typically contain 0.1 to 20 wt % of the stearidonic acid, or derivative, preferably 0.2 to 10 wt %.
According to another aspect of the invention there is provided a composition for oral ingestion to the human or animal body, comprising an oil extracted from the seeds of the Borignaceae family, or a physiologically acceptable derivative thereof, in combination with a physiologically acceptable carrier therefor.
The oil also has a wide range of dietetic uses. For example, the oil can be provided as an additive to existing food products, for instance as an additive to milk or milk-based drinks; it may form be in the form of a dietary supplement, or part of a dietary supplement (e.g. a vitamin-containing supplement), and may be provided in solid form, for example as a tablet, as a soft or hard gelatin capsule, or in liquid form, such as for parenteral use.
The amount of oil in the composition also depends upon the desired use. However, for most applications, an amount of the oil in the range of from 1 wt % and 20 wt % is appropriate.
The compositions according to the invention may be provided in a bottle, a tube or any other suitable packaging. The container for the compositions may be provided with dispensing means for dispensing the composition. Any known form of dispensing means may be used. When the composition is a liquid, it may be desirable to employ a dispensing means that can dispense it in the form of a spray.
We have described above the use of oil extracted from the seeds of the Borignaceae family, and compositions including such oils. This oil contains glycerides of a number of fatty acids, including stearidonic acid. However, it is possible to process the oil extracted from the seeds to to convert it at least partially to the corresponding fatty acids of the triglycerides in the oil. This processing would typically comprise a saponification to step to hydrolyse the triglycerides, an acidification step, and optionally at least one separation step to recover the stearidonic acid and other fatty acids. There may also be a purification step to purify the stearidonic acid so produced. Whilst any physiologically acceptable derivative of stearidonic acid may be used in the present invention, it is preferred that the derivative is an ester of stearidonic acid. More preferably the ester comprises an ester of stearidonic acid with an alcohol, particularly an ester of stearidonic acid with a polyol.
The present invention also includes the use of stearidonic acid formed from an oil extracted from seeds of the Borignaceae family in topical application to or for oral ingestion by, the human or animal body. The stearidonic acid so formed may be used alone for these purposes or, preferably, it is used to form part of a composition for topical application to or oral ingestion by, the human or animal body. The stearidonic acid may be part of a mixture of essential fatty acids formed from an oil extracted from the seed of the Borignaceae family.
According to another aspect of the invention there is provided the use of an oil according to the invention containing stearidonic acid or a physiologically acceptable derivative thereof, in a sunscreen composition.
According to another aspect of the invention there is provided the use of an oil according to the invention containing stearidonic acid or a physiologically acceptable derivative thereof, for the manufacture of a medicament for treating skin inflammation caused by burns.
According to another aspect of the invention there is provided the use of an oil according to the invention containing stearidonic acid or a physiologically acceptable derivative thereof, for the manufacture of a medicament for treating skin inflammation caused by exposure to UV radiation, or by exposure to sunlight.
According to another aspect of the invention there is provided a method treating skin inflammation caused by burns, comprising topically applying an oil according to the invention containing stearidonic acid, or a physiologically acceptable derivative thereof, to an inflamed area.
According to another aspect of the invention there is provided a method of treating skin inflammation cause by exposure to UV radiation or exposure to sunlight, comprising topically applying an oil according to the invention containing stearidonic acid, or aphysiologically acceptable derivative thereof, to an inflamed area.
According to another aspect of the invention there is provided the use of an oil according to the invention containing stearidonic acid or a physiologically acceptable derivative thereof, to inhibit the cyclo-oxygenase pathway.
According to another aspect of the invention there is provided the use of an oil according to the invention containing stearidonic acid or a physiologically acceptable derivative thereof, for the manufacture of a medicament for inhibiting the cyclo-oxygenase pathway.